Noradrenaline release Flashcards
What is the autonomic nervous system a part of?
The peripheral nervous system
What does the autonomic nervous system do?
Conveys all outputs from the CNS to the rest of the body except the motor innervation of skeletal muscle
What are the three divisions of the autonomic nervous system?
Sympathetic
Parasympathetic
Enteric
What does the autonomic nervous system regulate?
Smooth muscle tone All exocrine secretions Some endocrine secretions Heart rate and force Certain metabolic processes
What are the neurotransmitters of the parasympathetic nervous system?
Ach
Ach
What are the neurotransmitters of the sympathetic nervous system?
Ach
NAd
What is the first step of noradrenaline and adrenaline synthesis?
Tyrosine is converted to dihydroyphenylalanine
By tyrosine hydroxylase
What is the second step of noradrenaline/adrenaline synthesis?
Dihydroxyphenylalanine is converted to dopamine
By dopamine decarboxylase
What is the third stage of noradrenaline/adrenaline synthesis?
Dopamine is converted to noradrenaline
By dopamine beta hydroxylase
What is the fourth step of noradrenaline/adrenaline synthesis?
Noradrenaline is converted to adrenaline
By phenylethanolamine n-methyl transferase
Describe tyrosine hydroxylase
In the cytoplasm of catecholamine containing cells
Rate-limiting step
Feedback inhibition by NAd
Inhibited by alpha methyltyrosine
Describe dopamine decarboxylase
More widespread distribution
In cytoplasm
Inhibited by carbidopa
Describe dopamine beta hydroxylase
In catecholamine containing cells
In synaptic vesicles
Inhibited by nepicastat and etamicastat
Where is phenylethanolamine n methyl transferase found?
In A cells of adrenal medulla
What is alpha methyl tyrosine?
Inhibits tyrosine hydroxylase
Used in phaeochromocytoma
What is carbidopa?
Inhibits dopamine decarboxylase
Works in the periphery not CNS
Used in Parkinson’s
What is methyldopa?
Taken up by sympathetic neurones
Converted to alpha methylnoradrenaline
Displaces noradrenaline from vesicles
Used for hypertension in pregnancy
What is 6-OH dopamine?
Neurotoxin
Experimental use only
What is nepicastat?
Dopamine beta hydroxyls inhibitor
Used in cocaine dependence
What is etamicastat?
Dopamine beta hydroxyls inhibitor
Treating hypertension
Where are noradrenaline and adrenaline stored?
Adrenal glands
In chromaffin glands
What is reserpine?
Inhibits the vesicular amine transporter
Vesicular stores of catecholamine decrease
Previously used to treat hypertension
What triggers exocytosis from sympathetic nerves?
Ca2+ influx
What regulates the release of noradrenaline?
Sympathetic nerve terminals contain receptors for many mediators
Either facilitate or inhibit reduce of noradrenaline
What is autoinhibition?
Noradrenaline released from sympathetic varicosities acts on presynaptic receptors to inhibit its own release
Name some drugs that inhibit noradrenaline release
Acetylcholine
Adenosine
Opiods
Angiotensin
What are the side effects of morphine?
Constipation
Pupillary dilation
What are the two stages of termination of adrenaline and noradrenaline action?
Uptake
Degradation
How are catecholamines taken up?
Neuronal
Non-neuronal
How does neuronal uptake work?
Noradrenaline transporter
Co transports Na+ Cl- and catecholamine
What inhibits neuronal uptake?
Cocaine
Tricylic antidepressants
Phenoxybenzamine
How does non-neuronal uptake work?
Not particularly selective for noradrenaline
What inhibits non-neuronal uptake?
Normetanephrine
Steroid hormones
Phenoxybenzamine
How are catecholamines degraded?
By intracellular enzymes Monoamine oxidase Catechol-O-methyl transferase Aldehyde dehydrogenase Aldehyde reductase
What are noradrenergic neuron blocking drugs?
Inhibit noradrenaline release
e.g. guanethidine, bretylium
